This project aims to isolate and characterize putative endogenous tumor-promoters and to develop a rapid and economical assay for identification of exogenous and endogenous tumor-promoters. The following activities were specifically pursued: (1) To elucidate the mechanism of TPA induced inhibition of EGF binding (TIEB). To search for compound(s) which can reverse and modulate TIEB at non-toxic doses. (2) To isolate and characterize membrane receptors of phorbol esters. (3) To search for endogenous ligand(s) for phorbol receptors, isolate and characterize them. (4) To isolate and characterize growth factor(s) induced by biologically active phobol esters. (5) To test whether EGF and other growth factors enhance the carcinogenesis in-vivo and in-vitro. (6) To investigate whether TPA induces or enhances the expression of endogenous oncogenic cellular information. (7) To study whether retroviruses act as promoters in the carcinogenesis started by chemical or physical agents. (8) The reversal of anchorage independent growth of transformed cells by differentiation inducing agents.